Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals

Wei Liang; Kang Li; Haiyou Gao; Kunming Li; Jiansong Zhang; Qian Zhang; Xinying Jiao; Jialong Yang; Xiumei Wei

doi:10.24272/j.issn.2095-8137.2023.053

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Wei Liang, Kang Li, Haiyou Gao, Kunming Li, Jiansong Zhang, Qian Zhang, Xinying Jiao, Jialong Yang, Xiumei Wei. Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals. Zoological Research, 2024, 45(1): 13-24. doi: 10.24272/j.issn.2095-8137.2023.053

Citation:

Wei Liang, Kang Li, Haiyou Gao, Kunming Li, Jiansong Zhang, Qian Zhang, Xinying Jiao, Jialong Yang, Xiumei Wei. Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals. Zoological Research, 2024, 45(1): 13-24. doi: 10.24272/j.issn.2095-8137.2023.053

Citation:

Wei Liang, Kang Li, Haiyou Gao, Kunming Li, Jiansong Zhang, Qian Zhang, Xinying Jiao, Jialong Yang, Xiumei Wei. Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals. Zoological Research, 2024, 45(1): 13-24. doi: 10.24272/j.issn.2095-8137.2023.053

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Full T-cell activation and function in teleosts require collaboration of first and co-stimulatory signals

doi: 10.24272/j.issn.2095-8137.2023.053

Wei Liang^{1, #},
Kang Li^{1, #},
Haiyou Gao¹,
Kunming Li¹,
Jiansong Zhang¹,
Qian Zhang¹,
Xinying Jiao¹,
Jialong Yang^{1, 2
,
,},
Xiumei Wei^{1
,
,}

1.
State Key Laboratory of Estuarine and Coastal Research, School of Life Sciences, East China Normal University, Shanghai 200241, China
2.
Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Qingdao, Shandong 266237, China

Supplementary data to this article can be found online.
The authors declare that they have no competing interests.
W.L. designed and performed the experiments, analyzed the data, and drafted the manuscript. Kang L., H.G., Kunming L., J.Z., Q.Z., and X.J. performed the experiments. J.Y. and X.W. acquired funding, conceived the project, designed the experiments, analyzed the data, and drafted the manuscript. All authors read and approved the final version of the manuscript.
#Authors contributed equally to this work

Funds: This study was supported by the National Key Research and Development Program (2022YFD2400804), National Natural Science Foundation of China (32022086, 31972822), and Natural Science Foundation of Shanghai (20ZR1417500)

More Information

Corresponding author: E-mail: jlyang@bio.ecnu.edu.cn; xmwei@bio.ecnu.edu.cn
Received Date: 2023-05-06
Accepted Date: 2023-05-06

Published Online: 2023-09-09

Abstract

Abstract

Mammalian T-cell responses require synergism between the first signal and co-stimulatory signal. However, whether and how dual signaling regulates the T-cell response in early vertebrates remains unknown. In the present study, we discovered that the Nile tilapia (Oreochromis niloticus) encodes key components of the LAT signalosome, namely, LAT, ITK, GRB2, VAV1, SLP-76, GADS, and PLC-γ1. These components are evolutionarily conserved, and CD3ε mAb-induced T-cell activation markedly increased their expression. Additionally, at least ITK, GRB2, and VAV1 were found to interact with LAT for signalosome formation. Downstream of the first signal, the NF-κB, MAPK/ERK, and PI3K-AKT pathways were activated upon CD3ε mAb stimulation. Furthermore, treatment of lymphocytes with CD28 mAbs triggered the AKT-mTORC1 pathway downstream of the co-stimulatory signal. Combined CD3ε and CD28 mAb stimulation enhanced ERK1/2 and S6 phosphorylation and elevated NFAT1, c-Fos, IL-2, CD122, and CD44 expression, thereby signifying T-cell activation. Moreover, rather than relying on the first or co-stimulatory signal alone, both signals were required for T-cell proliferation. Full T-cell activation was accompanied by marked apoptosis and cytotoxic responses. These findings suggest that tilapia relies on dual signaling to maintain an optimal T-cell response, providing a novel perspective for understanding the evolution of the adaptive immune system.
- Oreochromis niloticus,
- CD3,
- CD28,
- T cells,
- Adaptive immunity,
- Evolution

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References(71)

References

[1]	Abelli L, Baldassini MR, Mastrolia L, et al. 1999. Immunodetection of lymphocyte subpopulations involved in allograft rejection in a teleost, Dicentrarchus labrax (L. ). Cellular Immunology, 191(2): 152−160. doi: 10.1006/cimm.1998.1430
[2]	Ai K, Li K, Jiao XY, et al. 2022. IL-2-mTORC1 signaling coordinates the STAT1/T-bet axis to ensure Th1 cell differentiation and anti-bacterial immune response in fish. PLoS Pathogens, 18(10): e1010913. doi: 10.1371/journal.ppat.1010913
[3]	Alcover A, Alarcón B. 2000. Internalization and intracellular fate of TCR-CD3 complexes. Critical Reviews in Immunology, 20(4): 325−346.
[4]	Anderson MK, Pant R, Miracle AL, et al. 2004. Evolutionary origins of lymphocytes: ensembles of T cell and B cell transcriptional regulators in a cartilaginous fish. The Journal of Immunology, 172(10): 5851−5860. doi: 10.4049/jimmunol.172.10.5851
[5]	Ashfaq H, Soliman H, Saleh M, et al. 2019. CD4: a vital player in the teleost fish immune system. Veterinary Research, 50(1): 1. doi: 10.1186/s13567-018-0620-0
[6]	Au-Yeung BB, Shah NH, Shen L, et al. 2018. ZAP-70 in signaling, biology, and disease. Annual Review of Immunology, 36: 127−156. doi: 10.1146/annurev-immunol-042617-053335
[7]	Bernard D, Riteau B, Hansen JD, et al. 2006. Costimulatory receptors in a teleost fish: typical CD28, elusive CTLA4. The Journal of Immunology, 176(7): 4191−4200. doi: 10.4049/jimmunol.176.7.4191
[8]	Beyersdorf N, Kerkau T, Hünig T. 2015. CD28 co-stimulation in T-cell homeostasis: a recent perspective. ImmunoTargets and Therapy, 4: 111−122.
[9]	Boardman T, Warner C, Ramirez-Gomez F, et al. 2012. Characterization of an anti-rainbow trout (Oncorhynchus mykiss) CD3ɛ monoclonal antibody. Veterinary Immunology and Immunopathology, 145(1-2): 511−515. doi: 10.1016/j.vetimm.2011.11.017
[10]	Bunnell SC, Diehn M, Yaffe MB, et al. 2000. Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade. Journal of Biological Chemistry, 275(3): 2219−2230. doi: 10.1074/jbc.275.3.2219
[11]	Bunnell SC, Singer AL, Hong DI, et al. 2006. Persistence of cooperatively stabilized signaling clusters drives T-cell activation. Molecular and Cellular Biology, 26(19): 7155−7166. doi: 10.1128/MCB.00507-06
[12]	Caporali R, Bugatti S, Cavagna L, et al. 2014. Modulating the co-stimulatory signal for T cell activation in rheumatoid arthritis: could it be the first step of the treatment?. Autoimmunity Reviews, 13(1): 49−53. doi: 10.1016/j.autrev.2013.06.008
[13]	Chappell WH, Steelman LS, Long JM, et al. 2011. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR inhibitors: rationale and importance to inhibiting these pathways in human health. Oncotarget, 2(3): 135−164. doi: 10.18632/oncotarget.240
[14]	Chen LP, Flies DB. 2013. Molecular mechanisms of T cell co-stimulation and co-inhibition. Nature Reviews Immunology, 13(4): 227−242. doi: 10.1038/nri3405
[15]	Cheng J, Montecalvo A, Kane LP. 2011. Regulation of NF-κB induction by TCR/CD28. Immunologic Research, 50(2-3): 113−117. doi: 10.1007/s12026-011-8216-z
[16]	Chitnis T, Kaskow BJ, Case J, et al. 2022. Nasal administration of anti-CD3 monoclonal antibody modulates effector CD8+ T cell function and induces a regulatory response in T cells in human subjects. Frontiers In Immunology, 13: 956907. doi: 10.3389/fimmu.2022.956907
[17]	Coppola C, Hopkins B, Huhn S, et al. 2020. Investigation of the impact from IL-2, IL-7, and IL-15 on the growth and signaling of activated CD4⁺ T cells. International Journal of Molecular Sciences, 21(21): 7814. doi: 10.3390/ijms21217814
[18]	Dickerson HW, Findly RC. 2017. Vertebrate adaptive immunity-comparative insights from a teleost model. Frontiers in Immunology, 8: 1379. doi: 10.3389/fimmu.2017.01379
[19]	Esensten JH, Helou YA, Chopra G, et al. 2016. CD28 costimulation: from mechanism to therapy. Immunity, 44(5): 973−988. doi: 10.1016/j.immuni.2016.04.020
[20]	Gimmi CD, Freeman GJ, Gribben JG, et al. 1993. Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation. Proceedings of the National Academy of Sciences of the United States of America, 90(14): 6586−6590.
[21]	Gorentla BK, Wan CK, Zhong XP. 2011. Negative regulation of mTOR activation by diacylglycerol kinases. Blood, 117(15): 4022−4031. doi: 10.1182/blood-2010-08-300731
[22]	Gorentla BK, Zhong XP. 2012. T cell receptor signal transduction in T lymphocytes. Journal of Clinical Immunology, 2012(S12): 5.
[23]	Green DR, Droin N, Pinkoski M. 2003. Activation-induced cell death in T cells. Immunological Reviews, 193(1): 70−81. doi: 10.1034/j.1600-065X.2003.00051.x
[24]	Hara T, Fu SM, Hansen JA. 1985. Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen). Journal of Experimental Medicine, 161(6): 1513−1524. doi: 10.1084/jem.161.6.1513
[25]	Hayden MS, Ghosh S. 2011. NF-κB in immunobiology. Cell Research, 21(2): 223−244. doi: 10.1038/cr.2011.13
[26]	Hu YH, Sun BG, Deng T, et al. 2012. Molecular characterization of Cynoglossus semilaevis CD28. Fish & Shellfish Immunology, 32(5): 934−938.
[27]	Janson ND, Jehanathan N, Jung S, et al. 2019. Insight into the molecular function and transcriptional regulation of activator protein 1 (AP-1) components c-Jun/c-Fos ortholog in red lip mullet (Liza haematocheila). Fish & Shellfish Immunology, 93: 597−611.
[28]	June CH, Ledbetter JA, Linsley PS, et al. 1990. Role of the CD28 receptor in T-cell activation. Immunology Today, 11: 211−216. doi: 10.1016/0167-5699(90)90085-N
[29]	Jung G, Ledbetter JA, Müller-Eberhard HJ. 1987. Induction of cytotoxicity in resting human T lymphocytes bound to tumor cells by antibody heteroconjugates. Proceedings of the National Academy of Sciences of the United States of America, 84(13): 4611−4615.
[30]	Jung JW, Lee AR, Kim J, et al. 2021. Elucidating the functional roles of helper and cytotoxic T cells in the cell-mediated immune responses of olive flounder (Paralichthys olivaceus). International Journal of Molecular Sciences, 22(2): 847. doi: 10.3390/ijms22020847
[31]	Jung JW, Lee JS, Kim YR, et al. 2017. Development of a monoclonal antibody against the CD3ε of olive flounder (Paralichthys olivaceus) and its application in evaluating immune response related to CD3ε. Fish & Shellfish Immunology, 65: 179−185.
[32]	Kuhns MS, Davis MM, Garcia KC. 2006. Deconstructing the form and function of the TCR/CD3 complex. Immunity, 24(2): 133−139. doi: 10.1016/j.immuni.2006.01.006
[33]	Laing KJ, Hansen JD. 2011. Fish T cells: recent advances through genomics. Developmental & Comparative Immunology, 35(12): 1282−1295.
[34]	Lesslauer W, Koning F, Ottenhoff T, et al. 1986. T90/44 (9.3 antigen). A cell surface molecule with a function in human T cell activation. European Journal of Immunology, 16(10): 1289−1296. doi: 10.1002/eji.1830161017
[35]	Li JQ, Liang W, Li K, et al. 2021. ZAP70 activation is an early event of T cell immunity that involved in the anti-bacterial adaptive immune response of Nile tilapia. Developmental & Comparative Immunology, 124: 104177.
[36]	Li K, Wei XM, Jiao XY, et al. 2023. Glutamine metabolism underlies the functional similarity of T cells between nile tilapia and tetrapod. Advanced Science, 10(12): e2201164. doi: 10.1002/advs.202201164
[37]	Li QT, Verma IM. 2002. NF-κB regulation in the immune system. Nature Reviews Immunology, 2(10): 725−734. doi: 10.1038/nri910
[38]	Liang W, Li KM, Zhang Q, et al. 2022. Interleukin-2 inducible T cell kinase (ITK) may participate in the anti-bacterial immune response of Nile tilapia via regulating T-cell activation. Fish & Shellfish Immunology, 127: 419−426.
[39]	Liu C, Xu XY, Han L, et al. 2020a. LRCH1 deficiency enhances LAT signalosome formation and CD8⁺ T cell responses against tumors and pathogens. Proceedings of the National Academy of Sciences of the United States of America, 117(32): 19388−19398.
[40]	Liu Y, Liu YE, Tong CC, et al. 2020b. CD28 deficiency attenuates primary blast-induced renal injury in mice via the PI3K/Akt signalling pathway. BMJ Military Health, 166(E): e66−e69. doi: 10.1136/jramc-2019-001181
[41]	Lu TZ, Liu X, Wu CS, et al. 2022. Molecular and functional analyses of the primordial costimulatory molecule CD80/86 and its receptors CD28 and CD152 (CTLA-4) in a teleost fish. Frontiers in Immunology, 13: 885005. doi: 10.3389/fimmu.2022.885005
[42]	Lu XJ, Chen J. 2019. Specific function and modulation of teleost monocytes/macrophages: polarization and phagocytosis. Zoological Research, 40(3): 146−150. doi: 10.24272/j.issn.2095-8137.2019.035
[43]	Marinari B, Costanzo A, Marzano V, et al. 2004. CD28 delivers a unique signal leading to the selective recruitment of RelA and p52 NF-κB subunits on IL-8 and Bcl-xL gene promoters. Proceedings of the National Academy of Sciences of the United States of America, 101(16): 6098−6103.
[44]	Mariuzza RA, Agnihotri P, Orban J. 2020. The structural basis of T-cell receptor (TCR) activation: an enduring enigma. Journal of Biological Chemistry, 295(4): 914−925. doi: 10.1016/S0021-9258(17)49904-2
[45]	Miyazawa R, Murata N, Matsuura Y, et al. 2018. Peculiar expression of CD3-epsilon in kidney of ginbuna crucian carp. Frontiers In Immunology, 9: 1321. doi: 10.3389/fimmu.2018.01321
[46]	Mu PF, Huo JY, Li XF, et al. 2022. IL-2 signaling couples the MAPK and mTORC1 axes to promote T cell proliferation and differentiation in teleosts. The Journal of Immunology, 208(7): 1616−1631. doi: 10.4049/jimmunol.2100764
[47]	Nguyen TD, Carrascal M, Vidal-Cortes O, et al. 2016. The phosphoproteome of human Jurkat T cell clones upon costimulation with anti-CD3/anti-CD28 antibodies. Journal of Proteomics, 131: 190−198. doi: 10.1016/j.jprot.2015.10.029
[48]	Nishibe S, Wahl MI, Hernandez-Sotomayor SM, et al. 1990. Increase of the catalytic activity of phospholipase C-γ1 by tyrosine phosphorylation. Science, 250(4985): 1253−1256. doi: 10.1126/science.1700866
[49]	Qin YT, Sun ZS, Wang W, et al. 2021. Characterization of CD3γ/δ⁺ cells in grass carp (Ctenopharyngodon idella). Developmental & Comparative Immunology, 114: 103791.
[50]	Randelli E, Buonocore F, Scapigliati G. 2008. Cell markers and determinants in fish immunology. Fish & Shellfish Immunology, 25(4): 326−340.
[51]	Ren Y, Liu SF, Nie L, et al. 2019. Involvement of ayu NOD2 in NF-κB and MAPK signaling pathways: insights into functional conservation of NOD2 in antibacterial innate immunity. Zoological Research, 40(2): 77−88. doi: 10.24272/j.issn.2095-8137.2018.066
[52]	Rodríguez-Caparrós A, Álvarez-Santiago J, DEL Valle-Pastor MJ, et al. 2020. Regulation of T-cell receptor gene expression by three-dimensional locus conformation and enhancer function. International Journal of Molecular Sciences, 21(22): 8478. doi: 10.3390/ijms21228478
[53]	Sanchez-Lockhart M, Kim M, Miller J. 2011. Cutting edge: a role for inside-out signaling in TCR regulation of CD28 ligand binding. The Journal of Immunology, 187(11): 5515−5519. doi: 10.4049/jimmunol.1102497
[54]	Sauerwein RW, Der Van Meer WG, Van Oostveen JW, et al. 1988. Anti-CD3 antibodies induce T helper function for human B cell differentiation in vitro by an interleukin 2-independent pathway. European Journal of Immunology, 18(1): 133−137. doi: 10.1002/eji.1830180120
[55]	Schwartzberg PL, Finkelstein LD, Readinger JA. 2005. TEC-family kinases: regulators of T-helper-cell differentiation. Nature Reviews Immunology, 5(4): 284−295. doi: 10.1038/nri1591
[56]	Sela M, Bogin Y, Beach D, et al. 2011. Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells. The EMBO Journal, 30(15): 3160−3172. doi: 10.1038/emboj.2011.213
[57]	Sloan-Lancaster J, Evavold BD, Allen PM. 1993. Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen-presenting cells. Nature, 363(6425): 156−159. doi: 10.1038/363156a0
[58]	Smith-Garvin JE, Koretzky GA, Jordan MS. 2009. T cell activation. Annual Review of Immunology, 27: 591−619. doi: 10.1146/annurev.immunol.021908.132706
[59]	Tafalla C, Leal E, Yamaguchi T, et al. 2016. T cell immunity in the teleost digestive tract. Developmental and Comparative Immunology, 64: 167−177. doi: 10.1016/j.dci.2016.02.019
[60]	Tang XQ, Qin YH, Sheng XZ, et al. 2017. Characterization of CD3⁺ T lymphocytes of Japanese flounder (Paralichthys olivaceus) and its response after immunization with formalin-inactivated Edwardsiella tarda. Fish & Shellfish Immunology, 63: 220–227.
[61]	Tavano R, Contento RL, Baranda SJ, et al. 2006. CD28 interaction with filamin-A controls lipid raft accumulation at the T-cell immunological synapse. Nature Cell Biology, 8(11): 1270−1276. doi: 10.1038/ncb1492
[62]	Wei XM, Ai K, Li HY, et al. 2019. Ancestral T cells in fish require mTORC1-coupled immune signals and metabolic programming for proper activation and function. The Journal of Immunology, 203(5): 1172−1188. doi: 10.4049/jimmunol.1900008
[63]	Wei XM, Li C, Zhang Y, et al. 2021. Fish NF-κB couples TCR and IL-17 signals to regulate ancestral T-cell immune response against bacterial infection. FASEB Journal, 35(4): e21457.
[64]	Wei XM, Zhang Y, Li C, et al. 2020. The evolutionarily conserved MAPK/ERK signaling promotes ancestral T-cell immunity in fish via c-Myc-mediated glycolysis. Journal of Biological Chemistry, 295(10): 3000−3016. doi: 10.1074/jbc.RA119.012231
[65]	Wilson AB. 2017. MHC and adaptive immunity in teleost fishes. Immunogenetics, 69(8-9): 521−528. doi: 10.1007/s00251-017-1009-3
[66]	Woodle ES, Thistlethwaite JR, Jolliffe LK, et al. 1991. Anti-CD3 monoclonal antibody therapy. An approach toward optimization by in vitro analysis of new anti-CD3 antibodies. Transplantation, 52(2): 361−368. doi: 10.1097/00007890-199108000-00034
[67]	Xing J, Liu WJ, Tang XQ, et al. 2021. The expression of CD28 and its synergism on the immune response of flounder (Paralichthys olivaceus) to thymus-dependent antigen. Frontiers in Immunology, 12: 765036. doi: 10.3389/fimmu.2021.765036
[68]	Yamaguchi T, Takizawa F, Furihata M, et al. 2019. Teleost cytotoxic T cells. Fish & Shellfish Immunology, 95: 422−439.
[69]	You L, Ren XX, Du YX, et al. 2016. c-Fos/ERK promotes the progression from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma. Oncology Reports, 36(6): 3413−3420. doi: 10.3892/or.2016.5169
[70]	Zhang YA, Hikima JI, Li J, et al. 2009. Conservation of structural and functional features in a primordial CD80/86 molecule from rainbow trout (Oncorhynchus mykiss), a primitive teleost fish. The Journal of Immunology, 183(1): 83−96. doi: 10.4049/jimmunol.0900605
[71]	Zhu MH, Janssen E, Zhang WG. 2003. Minimal requirement of tyrosine residues of linker for activation of T cells in TCR signaling and thymocyte development. The Journal of Immunology, 170(1): 325−333. doi: 10.4049/jimmunol.170.1.325